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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2011  |  Volume : 22  |  Issue : 4  |  Page : 751-756
Mucormycosis in renal transplant recipients: Predictors and outcome


1 Department of Nephrology and Clinical Transplantation, Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat, India
2 Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat, India

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Date of Web Publication9-Jul-2011
 

   Abstract 

Mucormycosis, though uncommon, is associated with high mortality in transplant recipients. This study was conducted to assess the incidence and risk factors associated with mucor infection and its outcome. We retrospectively reviewed the hospital records for evidence of mucor infection in patients transplanted between January 2005 and December 2009 at the Department of Nephrology and Clinical Transplantation (IKDRC), Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat, India. The patient demographics, symptoms, diagnostic techniques and outcomes were analyzed. Out of a total of 1,330 transplants, 16 patients (1.20%) had evidence of mucor infection, including 14 males and two females. The mean age of the patients was 43.8 years. The time interval between transplantation and disease onset varied greatly (range: 1 month to 7 years; median 13.8 months). The presenting symptoms were fever (87.5%), severe headache (56.2%), facial swelling (56.2%), watering of eyes (56.2%), cough (31.2%), respiratory distress (18.7%) and pain abdomen (12.5%). Suspected patients were evaluated by computerized tomographic (CT) scan/magnetic resonance imaging (MRI), bronchoalveolar lavage (BAL) and biopsy, and the diagnosis was confirmed by culture. Of the 16 patients studied, nine had rhinocerebral mucormycosis, five had pulmonary mucormycosis and one case each had infection at the graft anastmosis site and disseminated mucormycosis. Early and intensive treatment with liposomal amphotericin-B was instituted in all patients, and extensive debridement was performed in addition in 11 cases, and one patient was subjected to graft nephrectomy; 10 patients (62.5%) survived. Our study suggests that rhinocerebral is the most frequent site of mucormycosis and it can occur very early or late in the post-transplant period. Early diagnosis and combined surgical debridement and parenteral liposomal amphotericin-B along with reduction of immunosuppression improve the patient survival.

How to cite this article:
Godara S M, Kute V B, Goplani K R, Gumber M R, Gera D N, Shah P R, Vanikar A V, Trivedi H L. Mucormycosis in renal transplant recipients: Predictors and outcome. Saudi J Kidney Dis Transpl 2011;22:751-6

How to cite this URL:
Godara S M, Kute V B, Goplani K R, Gumber M R, Gera D N, Shah P R, Vanikar A V, Trivedi H L. Mucormycosis in renal transplant recipients: Predictors and outcome. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Oct 17];22:751-6. Available from: http://www.sjkdt.org/text.asp?2011/22/4/751/82678

   Introduction Top


Mucormycosis is a rare opportunistic fungal infection, most often caused by species of the genera Rhizopus, Rhizomucor and Cunnighamella. [1] In renal allograft recipients, it is an extremely rare condition with an incidence of 0.2-1.2%. [2],[3] It is a rapidly fatal complication, particularly if the patients had received aggressive anti-rejection therapy. [3],[4],[5],[6] Renal transplant recipients are at high-risk for mucormycosis because of chronic immunosuppression, frequent use of broad-spectrum antibiotics, and underlying metabolic disorders such as uremia and post-transplant diabetes mellitus (PTDM). [7] The most frequent form of presentation is believed to be rhinocerebral followed by pulmonary, disseminated and gastrointestinal infection. [8] The incidence of and mortality from invasive mycoses have increased in transplant patients. [9] Despite the increase in the number of renal transplantations being performed in India, there are limited data available on mucormycosis in these patients. Therefore, we conducted a retrospective study on 1,330 renal transplant recipients to determine the incidence, clinical presentation and mortality rate of mucormycosis in this group of patients. In this study, we report on 16 cases of mucormycosis after renal transplantation seen at the Department of Nephrology and Clinical Transplantation (IKDRC), Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat, India.


   Materials and Methods Top


This study was a single-center, retrospective study of renal transplant recipients, transplanted between January 2005 and December 2009. We reviewed the medical records of 16 of these patients diagnosed to have mucormycosis. Patients had been evaluated with respect to age, sex, date of transplantation, immunosuppressive regimen, graft rejection episodes, date of diagnosis, site of infection, treatment and outcome. Their maintenance immunosuppression regimen was cyclosporine A, mycophenolate mofetil and prednisolone. Suspicion of diagnosis was based on clinical presentation, radiological findings and unresponsiveness of infections to conventional antibiotic therapy. For cases suspected to have pulmonary involvement, fiber optic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) were performed.

The diagnosis of mucormycosis was made in the presence of at least one of the following criteria: a) histopathological evidence of tissue invasion on tissue biopsy; b) positive culture from a deep tissue specimen such as blood, cerebrospinal fluid (CSF), or biopsy specimen; and c) at least three positive sputum smears for pseudohyphae and budding yeast and/or positive sputum culture with clinical findings consistent with pneumonitis resistant to broad-spectrum antibiotics.


   Results Top


Out of the 16 patients studied, 14 (87.50%) were males and two (12.50%) were females. The mean age was 42 years (20-58 years). The symptoms related to mucormycosis began one month to nine years after transplantation (median, 14.8 months). They included fever (87.50%), cough (31.25%), respiratory distress (18.75%), severe headache (56.25%), facial swelling (56.25%) and watering of the eye(s) (56.25%). All patients were on immunosuppression therapy with cyclosporine A, mycophenolate mofetil and prednisolone. The final diagnosis was rhinocerebral mucormycosis in nine cases (56.25%) [Figure 1], pulmonary mucormycosis in five cases (31.25%) and disseminated mucormycosis and graft infection in one case each (6.25%). Upon diagnosis, all patients were treated with intravenous liposomal amphotericin-B. The initial dose was 1 mg/kg, which was gradually increased to 1-3 mg/kg with close observation for side effects. Simultaneously, the dose of the immunosuppressive drugs was reduced in all cases and discontinued in three cases. All patients with rhinocerebral mucor underwent surgery for debridement and the material was sent for histopathology [Figure 2]; additionally two patients underwent pulmonary resection and one underwent graft nephrectomy. The treatment modalities used caused improvement in 10 patients and six expired. [Table 1] illustrates the summary of patients' demographic, diagnostic and treatment characteristics.
Figure 1: CT scan of the para-nasal sinuses showing fungal mass in the left maxillary sinus.

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Figure 2: Histopathology of mucormycosis showing fungal hyphae (PAS ×200).

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Table 1: Characteristics of patients, diagnostic procedure, treatment modalities and final outcome.

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   Discussion Top


Renal transplant recipients are at a high risk of contracting opportunistic infections because of immunosuppresion with cytotoxic drugs and steroids, prolonged antibiotic therapy, granulocytopenia and metabolic factors such as uremia, hyperglycemia, and poor nutrition. [10],[11],[12],[13],[14] Mucormycosis refers to a spectrum of disease presentations caused by fungi of the class Zygomycetes, order Mucorales. These ubiquitous saprophytes are commonly found on decaying vegetation and in the soil. [2] These fungi grow rapidly and release large numbers of spores that can become airborne.

Although Zygomycetes are common in the environment, infection with this fungus is rare in humans due to the effectiveness of the intact human immune system. [4] Augmented immunosuppression to treat rejection, mainly in the form of steroids, as was given to our patients, may accelerate the course of mucormycosis infection. Furthermore, mucormycosis occurred more frequently in older recipients compared to younger patients. In our study, most of the patients were in their 40's and only five cases were under 40 years of age. In a retrospective study of fungal infection in hematopoietic stem cell transplant recipients, it was found that age >40 years was a risk factor for invasive fungal infection with mucormycosis. Also, other risk factors seen in our group of patients included induction therapy (87.5%), diabetes mellitus (DM) and PTDM (37.5%), rejection episodes (43.75%) and hepatitis C virus (HCV) infection (25%). The overall incidence rate in our series was 1.2% which could be because our study patients had multiple risk factors.

The predominant forms of presentation of mucormycosis are rhinocerebral, pulmonary, gastrointestinal, cutaneous and disseminated. The underlying medical condition and associated risk factors determine the type of mucormycosis that occurs in a patient. In patients with hematological malignancy, pulmonary mucor followed by disseminated and rhinocerebral presentations are the most common. [15] In our study, rhinocerebral mucormycosis was the most common form, accounting for more than 56% of all the infections. Similar reports has been published by Davari et al and Almyroudis et al, [16],[17] while Ahmadpour et al reported pulmonary infection to be the most prevalent type of mucormycosis in transplant recipients. [18] Pulmonary mucormycosis is a rapidly progressive infection that occurs after inhalation of spores into the bronchioles and alveoli. [19] Males appear to be over-represented in the medical literature, with a male to female ratio of 2.4-3:1; in the present study, this ratio for patients with rhinocerebral mucormycosis was 3.3:1. This could be because males generally outnumber females among the transplanted recipients. Disseminated mucormycosis involves two or more noncontiguous organs. The mortality rate for disseminated disease approaches 90-100% [20] and our patient with disseminated mucormycosis also died. Mucormycosis frequently occurs in the first year after renal transplantation, as seen in 68% of our patients. It is reported that 80% of cases of mucormycosis, in solid organ transplant recipients, occurred within the first six months of transplantation. [21] The prognosis of the rhinocerebral form is relatively poor [5] and it must be suspected in a transplant recipient having fever, maxillary swelling, and facial edema. Early diagnosis, aggressive surgical debridement, in conjunction with intravenous amphotericin-B and careful monitoring is helpful and is associated with a favorable prognosis. The mortality rate in the present series was low (33%), which could be due to early diagnosis and treatment in the form of surgery and use of liposomal form of amphotericin-B. Finally, primary mucormycosis of the renal allograft is a dreaded disease with grave prognosis. [22],[23] In our study, one patient had graft site mucormycosis. He died despite having undergone graft nephrectomy and using amphotericin-B due to sepsis and coagulopathy.

The strength of this study is that it may help to identify early post-renal transplant patients at high-risk of death from mucormycosis. Also, to our knowledge, this is the largest singlecenter study reported from India on mucormycosis in renal transplant patients.

The main limitation of this study is that this was a retrospective, single-center, observational study. Multi-center, prospective, controlled clinical trials are needed to further substantiate our observations.

In conclusion, mucormycosis is an extremely rare complication following kidney transplantation. Augmented immunosuppression, especially with corticosteroids, anti-rejection therapy, older age and PTDM are the main predisposing factors for the infection. A high index of suspicion, leading to an early diagnosis, may be the key to an early initiation of therapy.

 
   References Top

1.Glazer M, Nusair S, Breuer R, Lafair J, Sherman Y, Berkman N. The role of BAL in the diagnosis of pulmonary mucormycosis. Chest 2000; 117:279-82.  Back to cited text no. 1
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2.Chkhotua A, Yussim A, Tovar A, et al. Mucormycosis of the renal allograft: case report and review of the literature. Transpl Int 2001;14 (6):438-41.  Back to cited text no. 2
    
3.Nampoory MR, Khan ZU, Johny KV, et al. Invasive fungal infections in renal transplant recipients. J Infect 1996;33(2):95-101.  Back to cited text no. 3
    
4.Kauffman CA, Malani AN. Zygomycosis: an emerging fungal infection with new options for management. Curr Infect Dis Rep 2007;9(6): 435-40.  Back to cited text no. 4
    
5.Almyroudis NG, Sutton DA, Linden P, Rinaldi MG, Fung J, Kusne S. Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature. Am J Transplant 2006;6(10):2365-74.  Back to cited text no. 5
    
6.Aslani J, Eizadi M, Kardavani B, et al. Mucormycosis after kidney transplantations: report of seven cases. Scand J Infect Dis 2007;39(8): 703-6.  Back to cited text no. 6
    
7.Morduchowicz G, Shmueli D, Shapira Z, et al. Rhinocerebral mucormycosis in renal transplant recipients: report of three cases and review of the literature. Rev Infect Dis 1986;8 (3):441-6.  Back to cited text no. 7
    
8.Brown J. Zygomycosis: an emerging fungal infection. Am J Health Syst Pharm 2005;15: 62:2593-6.  Back to cited text no. 8
    
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10.Myerowitz RL, Medeiros AA, O'Brien TF. Bacterial infection in renal homotransplant recipients. A study of fifty-three bacteremic-episodes. Am J Med 1972;53:308-14.  Back to cited text no. 10
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15.Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis 2000;30(6):851-6.  Back to cited text no. 15
    
16.Davari HR, Malekhossini SA, Salahi HA, et al. Outcome of mucormycosis in liver transplantation: 4 cases and a review of literature. Exp Clin Transplant 2003;1:147-52.  Back to cited text no. 16
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17.Almyroudis NG, Sutton DA, Linden P, Rinaldi MG, Fung J, Kusne S. Zygomycosis in solid organ transplant recipients in a tertiary transplant centre and review of the literature. Am J Transplant 2006;6:2365-74.  Back to cited text no. 17
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18.Ahmadpour P, Lessan-Pezeshki M, Ghadiani MH, et al. Mucormycosis after Living Donor Kidney Transplantation: A Multicenter Retrospective Study. Int J Nephrol Urol 2009;1(1): 39-44.  Back to cited text no. 18
    
19.Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000;13(2):236-301.  Back to cited text no. 19
    
20.Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: areview of 929 reported cases. Clin Infect Dis 2005;41(5):634-53.  Back to cited text no. 20
    
21.Singh N, Gayowski T, Singh J, Yu VL. Invasive gastrointestinal zygomycosis in a liver transplant recipient: case report and review of zygomycosis in solid-organ transplant recipients. Clin Infect Dis 1995;20(3):617-20.  Back to cited text no. 21
    
22.Sajiv CT, Pawar B, Calton N, et al. Mucormycosis in renal allograft: a case report. Indian J Nephrol 2003;13:38-9.  Back to cited text no. 22
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23.Chugh KS, Sakhuja V, Jain S, et al. High mortality in systemic fungal infections following renal transplantation in third-world countries. Nephrol Dial Transplant 1993;8:168-72.  Back to cited text no. 23
[PUBMED]  [FULLTEXT]  

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Correspondence Address:
S M Godara
Department of Nephrology and Clinical Transplantation (IKDRC), Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat
India
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